Search

Purpose: To evaluate differences in diffusion parameters in thigh muscles in patients with glycogen storage disease type V (McArdle disease) using muscle diffusion tensor imaging (mDTI) compared to healthy controls METHODS: In this prospective study, we evaluated thigh muscles from hip to knee of 10 McArdle patients (5 female, mean age 33.7 ± 14.4 years) and 10 healthy age- and gender-matched volunteers. MRI scans were performed at 3 T and comprised mDTI, T1-weighted and T2-weighted imaging between May 2015 and May 2017. Needle biopsy of the vastus lateralis muscle was performed in three McArdle patients. The muscle tissue was analyzed by using histochemical and enzyme-histochemical techniques for glycogen content and histopathological changes. Mean values of the eigenvalues (λ1-λ3), fractional anisotropy (FA), and mean diffusivity (MD) were obtained for the vastus lateralis, vastus medialis, rectus femoris, biceps femoris, semitendinosus, and semimembranosus and compared between groups using Student's t tests, as well as ANCOVA; significance level was set at p < 0.05.Results: Needle biopsy showed intracellular glycogen accumulation in skeletal muscle fibers of three McArdle patients. Extracellular histopathological changes were not found. Muscle DTI analysis did not show statistically significant differences between patients and controls for any of the muscles.Conclusion: Despite intracellular glycogen accumulation in the three biopsy samples, mDTI parameters were not altered in McArdle patients compared to controls. We conclude that the currently used mDTI acquisition and processing lack the sensitivity to detect intracellular changes due to accumulated glycogen in this cohort of McArdle patients.Key Points: • Despite intracellular glycogen accumulation in three examined biopsy samples, mDTI parameters were not altered in McArdle patients compared to controls. • In its current form, diffusion MR does not provide additional information in quantifying intracellular glycogen accumulations within skeletal muscle fibers in McArdle patients. [ABSTRACT FROM AUTHOR]

Quantitative muscle MRI (qMRI) is a promising non-invasive method in the assessment of neuromuscular disorders. qMRI parameters are hypothesised to reflect histopathological changes in skeletal muscle tissue which was assessed in this study, employing the gold standard muscle biopsy. To evaluate the underlying histopathology leading to altered qMRI parameters, 26 patients (8 females, 46.4 ± 15.1 years, BMI 27.2 ± 4.1) were examined within 72 hours before and within 24 hours after a skeletal muscle biopsy using quantitative muscle MRI. Post-biopsy MRI was employed to pinpoint the exact localisation of the biopsy. qMRI parameters including intramuscular fat fraction (FF), water T2 relaxation time (T2), and diffusion metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (RD) were extracted from the localisation of biopsy from the first examination and correlated with histopathological findings. Additionally, three different segmentation masks were applied to the qMRI dataset to evaluate the potential differences between whole muscle analysis and region of interest analysis within the extracted muscle region. FF and T2 in qMRI correlated significantly with the FF in the muscle biopsy and histopathological inflammatory markers. FA correlated with the quantity of type 2 fibres, while MD correlated with p62. No differences were found using different segmentation masks in qMRI. In this study, we showed significant correlations of qMRI parameters for fat infiltration, inflammatory processes and fiber architecture properties with histopathological features in muscle biopsies, endorsing that qMRI serves as a suitable non-invasive method in the follow-up of patients with neuromuscular disorders, which verified the results from our previous study. Importantly, the absence of significant differences between segmentation masks suggests that whole muscle qMRI could reliably represent histopathology, useful when post-biopsy MRI is unavailable. [ABSTRACT FROM AUTHOR]

Skeletal muscle biopsy is one of the gold standards in the diagnostic workup of muscle disorders. By histopathologic analysis, characteristic features like inflammatory cellular infiltrations, fat and collagen replacement of muscle tissue or structural defects of the myofibers can be detected. In the past years, novel quantitative MRI (qMRI) techniques have been developed to quantify tissue parameters, thus providing a non-invasive diagnostic tool in several myopathies. This proof-of-principle study was performed to validate the qMRI-techniques to skeletal muscle biopsy results. Ten patients who underwent skeletal muscle biopsy for diagnostic purposes were examined by qMRI using a Philips 3T Achieva MR scanner and a 16CH Torso XL Coil. Fat fraction, water T2-time and diffusion parameters were measured in the muscle from which the biopsy was taken according to Schlaffke et al. 2017. The proportion of fat tissue, the severity of degenerative and inflammatory parameters and the amount of type 1- and type 2- muscle fibers were determined in all biopsy samples. The qMRI-data were then correlated to the histopathological findings. The amount of fat tissue in skeletal muscle biopsy correlated significantly with the fat fraction derived from the Dixon sequence. The water T2-time, a parameter for tissue edema, correlated with the amount of vacuolar changes of myofibers and endomysial macrophages in the histopathologic analysis. No significant correlations were found for diffusion parameters. In this proof-of-principle study, qMRI techniques were related to characteristic histopathologic features in neuromuscular disorders. The study provides the basis for further development of qMRI methods in the follow-up of patients with neuromuscular disorders, especially in the context of emerging treatment strategies. [ABSTRACT FROM AUTHOR]

With the promise of new treatments for Duchenne muscular dystrophy (DMD), there is a need for development of noninvasive biomarkers to assess pharmacologic response to study drugs. Magnetic resonance imaging (MRI) is a valuable tool for measuring the changes in the fat and water signal characteristics in dystrophic muscle. We performed a prospective imaging study of skeletal, cardiac, and respiratory muscles as part of a phase 2, placebo-controlled study of oligonucleotide GSK2401968-induced exon skipping in ambulatory boys with DMD. Muscles in the legs from the hips to the ankles were imaged using T1w, T2w, and 3-point Dixon sequences. Cardiac MRI measures of left ventricle (LV) mass, volume, thickness, fat/water quantitation of the myocardium, LV strain, stroke volume, and ejection fraction were also obtained. In addition, we applied recent and exploratory MRI methods including IDEAL/CPMG, diffusion weighted MRI, and dynamic breathing MRI for muscle fat and water quantitation, sarcolemmal disruption, and the dynamics of diaphragm movement and lung volume changes across the respiratory cycle, respectively. The MRI measures were compared between boys with DMD at baseline ( n = 13) and age range-matched healthy boys ( n = 20). A subset of DMD subjects ( n = 9) participated in the GSK2401968 study and had follow-up MRI studies at the 12, 24, and 48 weeks time points. All subjects underwent a standardized exercise of ankle dorsiflexion during each visit and had MRI of the lower leg muscles repeated after the exercise. The analysis of the imaging data is currently ongoing by blinded investigators and will be presented. [ABSTRACT FROM AUTHOR]